Abstract

Aim

While treatment options for SCC are limited, some pts derive modest benefit with erlotinib (E) or gefitinib (G). We previously reported interim data suggesting that A, an irreversible ErbB family blocker, had activity in pts with SCC (LL5, Part A). Subsequently, we demonstrated that continuation of ErbB blockade with A (plus P) in pts with non small cell lung cancer (NSCLC) progressing after benefit on E/G and A improved progression free survival (PFS),objective response rate (ORR) and disease control rate (DCR) vs IC (LL5, Part B). A pre-specified analysis of pts with SCC in LL5 is presented.

Methods

Pts with advanced NSCLC who failed ≥1 line of chemotherapy and E/G (after ≥12 wks benefit) were treated with A (50 mg/day; n = 1154; Part A). Upon progression on A (after >12 wks benefit), pts were randomized to receive A + P (40 mg/day, 80 mg/m2/week; n = 134) or IC (n = 68; Part B). The primary endpoint was PFS in Part B (RECIST 1.1).

Results

90 pts with SCC received A in Part A (median age: 63 years; male: 71%; East Asian: 31%; never smoked: 24%). Median PFS was 3.7 months, ORR was 6%, DCR was 60.0%. Seventeen pts met eligibility criteria for Part B randomization and were treated with A + P (n = 11) or IC (n = 6). Median PFS (8.8 vs 1.9 months; p = 0.003) and OS (14.9 vs 6.6 months; p = 0.433) were observed to be longer with A + P vs IC. ORR (45.5% vs 0.0%) and DCR (72.7% vs 16.7%) were both higher with A + P than IC. In Part A, diarrhea (83.3%; grade 3, 13.3%) and rash (60.0%; grade 3, 10.0%) were the most frequently reported adverse events (AEs) in pts with SCC. In Part B, 8 (72.7%) and 2 (40.0%) SCC pts experienced grade 3 AEs with A + P and IC, respectively. The most common AEs were asthenia (27.3%) and diarrhea (18.2%). 22.2% of pts discontinued A due to AEs (Part A); 27.3% of pts discontinued A+ P due to AEs (Part B).

Conclusions

In this small group of pts with SCC we observed prolonged PFS, higher OR and trend towards longer OS in patients treated with A + P vs IC following A. Such signs of activity with both A and A + P in this difficult-to-treat population are encouraging and warrant further investigation. AEs were similar to those observed in the whole trial.